MICROSOMAL IMMOBILIZED-ENZYME-REACTOR FOR ONLINE PRODUCTION OF GLUCURONIDES IN A HPLC COLUMN

被引:18
作者
ALEBICKOLBAH, T [1 ]
WAINER, IW [1 ]
机构
[1] MCGILL UNIV,MONTREAL GEN HOSP,DEPT ONCOL,DIV PHARMACOKINET,1650 CEDAR AVE,RMB 7113,MONTREAL H3G 1A4,QUEBEC,CANADA
关键词
COLUMN LIQUID CHROMATOGRAPHY; IMMOBILIZED-ARTIFICIAL-MEMBRANE (IAM) SUPPORT; MICROSOMAL IMMOBILIZED ENZYME REACTOR (IMER); GLUCURONIDATION;
D O I
10.1007/BF02274110
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Nonsolubilized rat liver microsomes have been noncovalently immobilized on an immobilized artifical membrane (IAM) HPLC chromatographic support to create a microsomal immobilized enzyme reactor (MIC-IMER). The MIC-IMER has been used for the on-line synthesis and analysis of Phase II metabolism conjugates. The activity of the MIC-IMER was investigated by following the in vitro glucuronidation of two well known UDP-glucuronosyltransferase (UDPGT; EC 2.4.1.17) substrates, 4-nitrophenol (4NP) and 4-methylumbelliferone (4Me7OHC). The substrates underwent conjugation with UDPGA and the rate of conjugation reaction in the MIC-IMER was compared, with the same reaction in the test-tube.
引用
收藏
页码:608 / 612
页数:5
相关论文
共 10 条
[1]   ENZYME-BASED HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY STATIONARY PHASES AS METABOLIC REACTORS - IMMOBILIZATION OF NON-SOLUBILIZED RAT-LIVER MICROSOMES ON AN IMMOBILIZED ARTIFICIAL MEMBRANE HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY SUPPORT [J].
ALEBICKOLBAH, T ;
WAINER, IW .
JOURNAL OF CHROMATOGRAPHY, 1993, 646 (02) :289-295
[2]   PROPERTIES OF HUMAN HEPATIC UDP-GLUCURONOSYLTRANSFERASES - RELATIONSHIP TO OTHER INDUCIBLE ENZYMES IN PATIENTS WITH CHOLESTASIS [J].
DRAGACCI, S ;
THOMASSIN, J ;
MAGDALOU, J ;
ELAMRI, HS ;
BOISSEL, P ;
SIEST, G .
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 1987, 32 (05) :485-491
[3]   SOLID-PHASE SYNTHESIS OF DRUG GLUCURONIDES BY IMMOBILIZED GLUCURONOSYLTRANSFERASE [J].
FENSELAU, C ;
PALLANTE, S ;
PARIKH, I .
JOURNAL OF MEDICINAL CHEMISTRY, 1976, 19 (05) :679-683
[4]   IMMOBILIZATION OF SOLUBILIZED UDP-GLUCURONOSYLTRANSFERASE FROM RAT-LIVER MICROSOMES TO SEPHAROSE-4B [J].
GILISSEN, RAHJ ;
MEERMAN, JHN ;
MULDER, GJ .
BIOCHEMICAL PHARMACOLOGY, 1992, 43 (12) :2661-2663
[5]   PHENOBARBITAL INDUCIBLE UDP-GLUCURONOSYLTRANSFERASE IS RESPONSIBLE FOR GLUCURONIDATION OF 3'-AZIDO-3'-DEOXYTHYMIDINE - CHARACTERIZATION OF THE ENZYME IN HUMAN AND RAT-LIVER MICROSOMES [J].
HAUMONT, M ;
MAGDALOU, J ;
LAFAURIE, C ;
ZIEGLER, JM ;
SIEST, G ;
COLIN, JN .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1990, 281 (02) :264-270
[6]  
HAUMONT M, 1991, APPL MICROBIOL BIOT, V35, P440
[7]  
LEHMAN JP, 1981, DRUG METAB DISPOS, V9, P15
[8]  
LOWRY OH, 1951, J BIOL CHEM, V193, P131
[9]  
MAGDALOU J, 1990, DRUG METAB DISPOS, V18, P692
[10]   IMMOBILIZED GLUCURONOSYLTRANSFERASE FOR SYNTHESIS OF CONJUGATES [J].
PARIKH, I ;
MACGLASHAN, DW ;
FENSELAU, C .
JOURNAL OF MEDICINAL CHEMISTRY, 1976, 19 (02) :296-299